Download - Raspa Infertility Final(Optimized)
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Objectives:
List the common causes of male and female
infertility
Begin an infertility evaluation, ordering initialtests
Prescribe simple treatments for infertile
couples Facilitate appropriate referral to infertility
specialists
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Infertility:
Inability to conceive after 12 months of
frequent, unprotected intercourse
Some however begin initial work-up after 6months as the fecundability (ability to
conceive) decreases as times passes,
particularly if history suggests infertility or if
female partner older than 35 (decreased
ovarian function)
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Is infertility common?
10-15% of couples in the US
1.2 million women visited their primary caredoctor for infertility in 2002
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Risk Factors
Smokingdecreased conception
Alcoholincreased infertility
Stress (acupuncture helps)
IUD removaltakes longer to conceive
Increased agefathers over 40
Gulf war vets
Inflammatory bowel disease
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Other Factors
No increased risk with male underwear type
or
Ruptured appendix Unknown effects of environmental
estrogensPCBs
Nifedipine may decrease male fertility?
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Timing Factors
Sperm live 48-72 hours
Eggs live 12 hours
Fertility Focused Intercourse is important
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Etiology:
Male: 20%
Female: 38%
Mixed: 27%
Unexplained: 15%
Importance of evaluation of both partners
WHO 1982-1985 multi-center study
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Causes of Female Infertility
Ovulation disorders-25%
Endometriosis-25%
Pelvic Adhesions-12%
Tubal Blockage-11%
Other Tubal Factors-11%
Hyperprolactinemia-7%WHO Technical Report Series 1992
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Female Causes:
Cervical factorsbad mucus, antibodies, infection
Uterine Factorssubmucosal fibroids, bicornuate
uterus, Ashermans syndrome
Tubal factorsPID, endometriosis, post-op
adhesions
Ovary Factorsanovulation, luteal phase defect,
toxins (chemotherapy) Bad eggschromosomal (Turners Syndrome)
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Female H&P:
Gs and Ps
PMH including STD Hx
Medications
Substance Use Menstrual Hx
Age at onset? Regular? Duration? Premenstral Sx?
Endometriosis Sx: dysmenorrhea, dyspareunia,
Endocrine Sx: galactorrhea, hirsuitism, fatigue,constipation, weight gain, etc
Exercise
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Female H&P:
Physical Exam:
Vitals, BMI
Skin: Acne, hirsuitism
Thyroid: enlargement
Breast: galactorrhea, development
Pelvic: uterine size, tenderness, discharge,
masses, development
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Initial Counseling:
Frequency and timing of intercourse
Fertile Interval: 5 days preceding ovulation and day of
ovulation
Smoking Alcohol
Caffeine
Stress Body weight (Ideal BMI is 20-25)
Prenatal vitamins
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Initial Female Work-Up:
Ovulation???:
Regular Menses with Premenstrual Sx:
Some confirm ovulation by history/chartingalone
Irregular Menses or desire confirmation:
Charting
Progesterone on cycle day 21
LH surge (home urinary kits)
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Charting:
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Menstrual Cycle:
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Ovulation Disorders:
WHO Classification:
1: Hypogonadotropic Hypogonadal
5-10%
2: Normogonadotropic Normoestrogenic
70-85%
Includes PCOS
3: Hypergonadotropic Hypoestrogenic 10-30%
Hyperprolactinemia
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Anovulation:
Determination of cause/class:
FSH/LH
Estradiol (E2)
Progesterone
Prolactin/TSH
Comprehensive Metabolic Panelliver, renal
Testosterone, Androstenedione, DHEA-S,
17-OH Progesterone
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Class 1 Anovulation:
Hypogonadotropic Hypogonadal Low FSH and low estradiol
Due to either decreased hypothalamic secretion
of GnRH (Kallmans) or pituitary insensitivity toGnRH
Results in decreased pituitary release of FSH
FSH stimulates follicular maturation and thus
estradiol secretion
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Class 1 Treatment:
Gonadotropins (FSH/LH)
Indications:
Class 1 anovulatory pts Class 2 anovulatory pts who have failed initial tx
Risks:
Multiple gestations Ovarian hyperstimulation
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Class 1 Treatment:
Gonadotropins (FSH/LH)
Dose:
Step-up vs Step-down protocols Monitoring:
Transvaginal US q2-3 days to monitor follicles
and timing of hCG dose to induce ovulation of
dominant follicle
Given by Reproductive Endocrinologists
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Class 2 Anovulation:
Normogonadotropic Normoestrogenic:
Normal levels of FSH and estrodiol
FSH secretion during follicular phase is sub-
normal
May ovulate intermittently, particularly if have
oligomenorrhea
Causes: PCOS, Hyperthyroidism, Androgenichormones from tumors, liver or renal disease,
Cushings (work-up is here)
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Treatment of Class 2 Anovulation:
Check lab results from anovulatory work upand treat as appropriate
PCOS: increased BMI, hirsuitism, anovulation,
2:1 LH:FSH ratio Best treatment is achieve ideal body weight
or at least a 10% reduction in wt.
Best BMI 20-25 Low body wt or high stress decreases
GnRH, can be like WHO 1 .
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Class 2 Treatment: Metformin
Improves insulin insensitiviy
Restores ovulation in 50% of PCOS
Titrate dose to minimize side effects
Minimal effect on hirsuitism Trial for 6 months with continued charting to eval
for ovulation
Not FDA approved for combo with Clomiphene butsome trials have shown benefit of combo whileothers show similar success rates as Clomiphenealonecombined effect 60% preg rate in PCOS
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Class 2 Treatment: Clomiphene
Induces ovulation by increased gonadotropinrelease
Dose: 50mg days 5-9; up to 100mg daily if needed
Intercourse timing and frequency; +/- urine LH kit +/- Metformin (PCOS)
+/- Intrauterine Insemination (cervical factors)
6 cycles max
Letrazole is alternative with similar efficacy to
Clomiphene
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Class 2 Treatment: Aromatase
Inhibitors Block final step of estrogen synthesis
Letrozol 2.5 - 5mg daily on days 3-7
(anastazol) or 25mg once day 3.
Intercourse timing and frequency; +/- urineLH kit
Similar efficacy to clomiphene
Minimal side effects
Lower incidence of multiple gestations
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Class 3 Anovulation:
Hypergonadotropic Hypoestrogenic:
High FSH and low estradiol
FSH is inappropriately high due to lack of
negative feedback from estradiol
Causes: Premature ovarian failure or Ovarian
resistance
Resistant to treatment
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Class 3 Anovulation:
Rare
Poor Prognosis--best test is Antimullerian
Hormonehigh is good, less than 2.5 is bad Clue given with Clomiphene Challenge Test
Test FSH on Day 3
Clomiphene Day 5-9 Test FSH on Day 10
If either FSH greater than 10, reduced ovarian
function.
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Anovulatory Treatment Overview:
WHO Class 1: GnRH problemtreat with
GnRH pump and support (Not available in
US) or Gonadotropins (Refer)
WHO Class 2: Most patients herewe can
treat
WHO Class 3: Ovarian failurelittle hope
with any therapy (Refer)
Hyperprolactinemia: RxDrugs or Surgery
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Regular Menses:
Ovulatory cycles confirmed by:
Charting x 3 months
Cycle day 21 Progesterone
LH surge
Fertility focused intercourse
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Ovulation confirmed:
Lifestyle changes
Chlamydia/GC test
Male partner testing
Good Cervical Mucus Mucus enhancermucinex, vit B6
Increase mucus with antibiotics day 9-14
Prolactin, TSH
Luteal phase defect? < 10 days
Fertility focused intercourse x 3 months
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Further work-up:
Check Hysterosalpingogram (HSG)
Tubal factors: patency
Uterine factors: anatomy, submucosal fibroids
Oil based contrast has a good track record ofpregnancy after HSG
If 3 more months go by will need laparoscopy to
check for endometriosis, adhesions, ovarianproblems (hydrosalpinges)
Key to treatment is find the problem and treat
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Male Infertility
Male factor infertility 20% of couples
Contributes to 30-40%
Azoospermiano sperm
Aspermiano semen
Oligospermiadecreased normal sperm
Need 2 sperm samples after 48-72 hourabstinence say experts
AUA and ASRM Practice Committee Reports2001
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Male Infertility
Pre-testicularendocrinetreatablerare
Testicularspermatogenesisuntreatableexcept varicoceles
Post-testicular40% obstruction
History
Mumps, Trauma, Infection, Chemo, Radiation,
HeatUnderwear doesnt matter Family History?
Prior Fertility?
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Male Workup
Exam
Male secondary sex characteristics
Assure vas deferens bilaterally
Testis size
Varicocele
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Sperm Count
FertileOver 48 million, Over 63% motile,
Over 12% normal morphology
Likely Not FertileLess than 13.5
million,Less than 32% motile, Less than 9%
normal morphology
In the middleindeterminateNew England J Med 2001:345:1388
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Lab Workup
Abnormal semen--
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Male Causes
Absense of vas deferens
Renal agenesis in 10-20%
Cystic Fibrosismost will have congenital
bilateral absence of vas deferens
CFTR mutationif positive, check female
Bilateral testicular atrophy
Low FSH and TKallman or Pituitary tumor
Check prolactin and MRI
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Duct Obstruction
May be treatable
If normal volumeeither disordered
spermatogenesis or near testicular
obstruction
If FSH upspermatogenesis problem
If FSH is normal, biopsy testis
Low sperm volumeejaculatory dysfunction
Consider TRUS
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Azoospermia
Check chromosome7% abnormal
2/3 Klinefelters XXY
Microdeletions on Y chromosome seen with
PCR, not on karyotype
Assay when non-obstructive oligospermia with
sperm less than 5 million
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Unexplained Infertility
Most likely combined male and female
factors
Treatments are multiple but many
unsatisfying
Time alone may be treatment or
Refer
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Advanced Reproductive
Technologies (ART)
Most deliver normal infants
BUT: Infertility treatment associated with
increased risk of adverse pregnancy
outcomes
Placental abruption, fetal loss 2nd trimester,
preeclampsia, previa, C/S, ovarian torsion
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Advanced Reproductive
Technologies (ART)
Multiple births and birth defects, preterm
and low birth weight, cerebral palsey
Insufficient evidence regarding risks and
benefits for IVF for unexplained infertility
18-22% success per cycle
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Other Drugs
Metformin may induce ovulation inanovulatory women withouthyperandrogenism
ASA doesnt help Testosterone doesnt help for males
Ginseng may help increase sperm count
and motility Chasteberry associated with increased
pregnancy ratelevel 2 evidence
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Other considerations
Intrauterine insemination (IUI) better if
antibodies or if subfertile male
As effective, cheaper, and safer than IVF for
idiopathic infertilityLancet 2000
Varicocele repair probably doesnt help
FSH (HCG) therapy for subfertilitymixedresults
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Pregnancy Support:
After conception progesterone
supplementation has been shown to be
effective in reducing miscarriage,
preeclampsia and preterm birthin IVF andwithout
Can use HCG as wellstimulates estrogen
and progesterone
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Pregnancy Support:
Counselinggroupimproved pregnancy
rate
Accupuncture works for IVFlikely works
for normal conception if stress is an issue
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Summary:
Consider causes of infertility
Do systematic workupovulatory vs non-
ovulatory
If ovulatory, consider tubal and male factors
Find the cause and treat.
Refer when unable to find cause or if unableto perform treatment
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Questions?